Liposomes have proved a valuable tool for delivering various pharmacologically active molecules, such as anti-neoplastic agents, to cells, organs, or tumors. However, it has been found that deposition of liposomes into tumors can be highly variable between not only tumors of different subtypes between patients, but also between tumors of similar subtype within the same patient. The outcome of treatment with liposomally-delivered therapeutic agents can therefore be somewhat unpredictable for a given patient.
Liposome delivery has been shown to improve the pharmacokinetic profile and widen the therapeutic index of certain anticancer drugs, especially the anthracycline class. Improved efficacy is in part a result of passive targeting to tumor sites based on the enhanced permeability and retention (EPR) effect. To fully exploit this process, drug carriers should be engineered to retain drug while circulating, thereby preventing premature drug release before accumulating in the tumor but still allowing for release of drug once in the vicinity of the tumor. Antibody-targeted nanoparticles, such as immunoliposomes against HER2 or epidermal growth factor receptor, represent another strategy for more efficient drug delivery to tumor cells.
It has been found, however, that deposition of liposomal drugs into tumors varies. Tumors that have higher drug deposition will have improved clinical outcomes. Liposomal drugs have been shown to enter tumors via a mechanism termed the enhanced permeability and retention (EPR) effect whereby liposomes can preferentially escape from the bloodstream into the tumor interstitium via leaky tumor vasculature and then become trapped in the tumor by virtue of their large size and the lack of functional lymphatics. However, the degree to which liposomal particles can deposit into tumors has been shown to be highly variable in both preclinical tumor models and in clinical studies whereby liposomes have been used as imaging agents to quantify the level and variability of tumor deposition. The invention provides liposomal imaging agents that can be used to predict which patients' tumors will have low or high deposition of liposomal drugs and ultimately which will benefit from a particular liposomal drug.
Non-invasive methods for determining whether a liposomally-delivered therapeutic agent is suitable for use in a patient before treatment (e.g., to predict clinical outcomes of targeted and untargeted liposomal therapeutics) are therefore needed.